Document Detail


Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma.
MedLine Citation:
PMID:  20232393     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tumor metastasis is the dominant cause of death in cancer patients, including patients with oral tongue squamous cell carcinoma (TSCC). Previously, we reported that reduced miR-138 level is correlated with enhanced metastatic potential in TSCC cells. Here, we demonstrate that miR-138 suppresses TSCC cell migration and invasion by regulating 2 key genes in the Rho GTPase signaling pathway: RhoC and ROCK2. Direct targeting of miR-138 to specific sequences located in the 3'-untranslated regions of both RhoC and ROCK2 mRNAs was confirmed using luciferase reporter gene assays. Ectopic transfection of miR-138 reduced the expression of both RhoC and ROCK2 in TSCC cells. These reduced expressions, in consequence, led to the reorganization of the stress fibers and the subsequent cell morphology change to a round bleb-like shape as well as the suppression of cell migration and invasion. In contrast, knockdown of miR-138 in TSCC cells enhanced the expression of RhoC and ROCK2, which resulted in an altered, elongated cell morphology, enhanced cell stress fiber formation and accelerated cell migration and invasion. Taken together, our results suggest that miR-138 plays an important role in TSCC cell migration and invasion by concurrently targeting RhoC and ROCK2, and miR-138 may serve as a novel therapeutic target for TSCC patients at risk of metastatic disease.
Authors:
Lu Jiang; Xiqiang Liu; Antonia Kolokythas; Jinsheng Yu; Anxun Wang; Caroline E Heidbreder; Fei Shi; Xiaofeng Zhou
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  127     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-07-05     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  505-12     Citation Subset:  IM    
Affiliation:
Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Carcinoma, Squamous Cell / pathology*
Gene Knockdown Techniques
Humans
MicroRNAs / physiology*
Neoplasm Invasiveness / physiopathology*
Neoplasm Metastasis / physiopathology*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction*
Tongue Neoplasms / pathology*
rho GTP-Binding Proteins / genetics,  metabolism*
rho-Associated Kinases / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
K22 DE014847-05/DE/NIDCR NIH HHS; K22 DE014847-05S1/DE/NIDCR NIH HHS; K22DE014847/DE/NIDCR NIH HHS; R01CA139596/CA/NCI NIH HHS; R03 CA135992-01A1/CA/NCI NIH HHS; R03 CA135992-02/CA/NCI NIH HHS; R03CA135992/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/MicroRNAs; 0/RHOC protein, human; 0/RNA, Messenger; 0/ROCK2 protein, human; EC 2.7.11.1/rho-Associated Kinases; EC 3.6.5.2/rho GTP-Binding Proteins
Comments/Corrections

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